Chronic ethanol induces changes in opiate receptor function and in met-enkephalin release

Area of Science:

• Neuroscience
• Pharmacology
• Biochemistry

Background:

• Ethanol consumption is known to affect the central nervous system.
• Opioid receptors, including delta and mu subtypes, play crucial roles in regulating various physiological processes.
• Enkephalins are endogenous opioid peptides that modulate pain and reward pathways.

Purpose of the Study:

• To investigate the effects of chronic ethanol consumption on striatal delta- and mu-opiate receptor binding.
• To elucidate the mechanisms underlying ethanol-induced changes in opioid receptor sensitivity.
• To explore the potential role of endogenous ethanol metabolites in modulating opioid receptor function.

Main Methods:

• Radioligand binding assays using 3H-Etorphine, 3H-Met-enkephalin, and 3H-DHM to label delta and mu-opiate receptors.
• Measurement of enkephalin release from striatal slices.
• In vitro studies using salsolinol to assess its interaction with opioid receptors.

Main Results:

• Chronic ethanol consumption induced supersensitivity of striatal delta-opiate receptor sites.
• A diminished enkephalin release was observed in striatal slices from ethanol-fed rats.
• Kd values for 3H-Met-enkephalin and 3H-DHM binding (mu-opiate receptors) were enhanced, indicating decreased affinity.
• In vitro studies confirmed that salsolinol, an ethanol metabolite, acts as a mu opioid agonist, displacing 3H-Met-enkephalin and 3H-DHM binding but not 3H-DADLE binding.
• Delta-receptors appeared to become supersensitive due to decreased endogenous peptide release.

Conclusions:

• Ethanol differentially affects delta- and mu-opiate receptors, likely through specific impacts on enkephalinergic transmission.
• The observed decrease in mu-opiate receptor affinity may be attributed to endogenous ethanol metabolites like salsolinol acting as agonists.
• Delta-receptor supersensitivity is likely a consequence of reduced endogenous enkephalin release.